In a 2017 article in the journal Psychological Medicine, researcher Marta Rapado-Castro and colleagues reported that among 58 patients with bipolar disorder or schizophrenia and symptoms of psychosis, those who took two grams per day of the antioxidant n-acetylcysteine (NAC) showed improvements in working memory after six months compared to those who took placebo over the same study period.

Antipsychotic medications can typically reduce psychotic symptoms such as delusions or hallucinations, but cognitive symptoms such as problems with learning, memory, or information processing may remain. NAC, which is sold over-the-counter as a nutritional supplement, seemed to improve these symptoms.

The researchers suggest that larger studies of NAC are needed, particularly to determine whether giving NAC to patients during their first episode of psychosis could prevent cognitive decline from occurring at all during the course of their illness.

NAC has been found to have a range of benefits, including reducing substance abuse and interfering with habit-based behaviors such as compulsive hair-pulling, obsessive-compulsive disorder, and gambling.
Researcher Michael Berk, a co-author of the study, reported in the journal Biological Psychiatry in 2008 that NAC could also improve depressive symptoms in bipolar disorder and negative symptoms in schizophrenia.

Editor’s Note: Since cognitive deficits are common in both schizophrenia and bipolar disorder, using NAC in addition to antipsychotic medications could be a useful tool to address these types of symptoms.

Some people have found that gluten-free or casein-free diets have improved their intestinal, autoimmune, or neurological symptoms. (Casein is a protein found in mammals’ milk. Cow milk is high in casein while human milk proteins are 20–45% casein.) One explanation for the good effects of these diets is that peptides that are released during digestion of these foods can create epigenetic changes in gene expression, adding methyl groups to DNA strands that increase inflammation.

As infants transition from getting all of their nutrition from the placenta to using their gastrointestinal tract, their diet may lead to epigenetic modifications that affect their health later in life. Epigenetics refers to changes in genes that do not affect the inherited sequence of DNA, but affect how easily the DNA is transcribed to produce proteins. Methyl or acetyl groups can be added to DNA or the histones around which it is wound.

When a person digests casein (from either human or animal milk) or gliaden (a protein derived from wheat), peptides are released that activate opioid receptors, modulating the uptake of the amino acid cysteine in neurons and in the gastrointestinal tract. This decrease in cysteine uptake is associated with drop in the antioxidant glutathione and a methyl donor (a molecule with a reactive methyl group that can easily become part of another molecule) called S-Adenosyl methionine.

In addition to decreasing cysteine uptake, the peptides also increase DNA methylation and create epigenetic changes in genes involved in redox (changes in oxidation) and methylation homeostasis.

These processes are described in a 2014 article by Malav S.Trivedi et al. in the Journal of Nutritional Biology. Trivedi et al. conclude that milk and wheat can change antioxidant activity and gene expression. Differences in the peptides in human and cow milk may explain developmental differences between children who are breastfed and those who receive formula.

The decrease in antioxidants caused by peptides from wheat and milk can predispose people to inflammation and oxidation, explaining why wheat- or casein-free diets might be useful.

Very dark chocolate made mostly from cocoa beans may be good for you. Cocoa is high in flavanols, which belong to a class of antioxidants called flavonoids. Dark chocolate has been associated with lowered risk of heart attack and stroke, improvements in cognition, lower body mass index (BMI, a weight to height ratio), dilation of blood vessels and lower blood pressure, and improved cholesterol profiles. This is despite containing a lot of saturated fat (a good trick, indeed). Among a study of 37,000 Swedish men, individuals who ate at least 1.8oz of dark chocolate a week had a 17% lower risk of stroke than those who ate less than 0.4oz a week.

Moderation is important. Two ounces of dark chocolate contain about 440 calories, so while a little may be good, a lot may not be so good. Watch out for milk chocolate and highly processed chocolates with great quantities of sugar added, they contain more calories and fewer health benefits.

A balanced diet and regular exercise are keys to good health, but don’t feel too badly if you top off a balanced meal with a tantalizing piece of the dark stuff.

In a poster at the 9th International Conference on Bipolar Disorder (ICBD) held in Pittsburgh in 2011, Guy Goodwin and colleagues reported that relative to controls, blood from patients with bipolar disorder contained more total glutathione, a potent antioxidant, and a higher ratio of oxidized to reduced glutathione. Measurements of blood glutathione could eventually serve as a biomarker, suggesting when a diagnosis of bipolar disorder is likely.

Editor’s note: Glutathione is one of the major antioxidants in humans. Oxidized glutathione is a less active form, so the higher levels of oxidized glutathione compared to reduced glutathione in patients with bipolar disorder suggests they may have a relative deficiency of the active form. These data are consistent with reports that patients in manic and depressive phases of bipolar disorder have increased oxidative stress and free radicals that impair cellular functioning.

Together,these results highlight the potential utility of treatments that increase antioxidant activity. One option is N-acetylcysteine (NAC), which the body converts into glutathione. As previously noted in the BNN, Michael Berk reported in Biological Psychiatry in 2008 that NAC (1000 mg twice a day) appears to exert greater antidepressant effects over a period of 24 weeks than placebo when added into previously ineffective regimens in patients with bipolar disorder.

In another poster at the conference, Magalhaes and colleagues reported on NAC treatment for a subgroup of the bipolar patients in the study by Berk who were in a major depressive episode at the time of the study. They found that NAC had highly significant acute antidepressant effects of large magnitude in this subgroup of patients.

The glutathione data by Goodwin et al. provide a further rationale for consideration of the use of NAC in bipolar disorder, particularly in the acute and longer-term treatment of the depressive phases. As we reported in BNN Issue 1 from 2010, NAC also exerts positive effects in many illnesses that commonly occur comorbidly with bipolar disorder. These include cocaine and heroin addiction, gambling addiction, obsessive compulsive disorder (as an adjunct to selective serotonin reuptake inhibitors (SSRIs)), and trichotillomania (compulsive hair-pulling).

Although the editors of BipolarNews.org have made every effort to report accurate information, much of the work referenced here is in abstract or pre-publication form, and may not have received proper review by the scientific community at this time. Patients should consult with their physicians about any treatment decisions. Physicians should consult the peer-reviewed literature.